Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
J Cell Mol Med. 2023 Jun;27(11):1477-1492. doi: 10.1111/jcmm.17748. Epub 2023 Apr 19.
Our group have demonstrated that splenic B cells contributed to the CD4 CD25 naive T cells conversion into CD4 CD25 Foxp3 regulatory T cells without adding appended cytokines, named Treg-of-B cells which were potent suppressors of adaptive immunity. We like to investigate whether Treg-of-B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co-cultured the bone marrow-derived macrophages (BMDMs) with Treg-of-B cells under LPS/IFN-γ stimulation and analyzed the M2-associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg-of-B cell-induced M2 macrophage for skin inflammation using imiquimod (IMQ)-induced psoriatic mouse model. Our results showed that BMDMs co-cultured with Treg-of-B cells upregulated typical M2-associated molecules, including Arg-1, IL-10, Pdcd1lg2, MGL-1, IL-4, YM1/2 and CD206. In an inflammatory environment, TNF-α and IL-6 production by macrophages co-cultured with Treg-of-B cells was decreased significantly. The molecular mechanism revealed that Treg-of-B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact-dependent manner. Moreover, the treatment with Treg-of-B cell-induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ-induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg-of-B cell-induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3 Treg-of-B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell-based therapeutic strategy for psoriasis.
我们的研究小组已经证明，脾 B 细胞有助于 CD4 CD25 幼稚 T 细胞在不添加附加细胞因子的情况下转化为 CD4 CD25 Foxp3 调节性 T 细胞，我们将其命名为 Treg-of-B 细胞，它是适应性免疫的有效抑制物。我们想研究 Treg-of-B 细胞是否可以促进替代激活的巨噬细胞（M2 巨噬细胞）极化并缓解炎症性疾病，如银屑病。在这项研究中，我们在 LPS/IFN-γ 刺激下将骨髓来源的巨噬细胞（BMDM）与 Treg-of-B 细胞共培养，并使用 qPCR、western blot 和免疫荧光染色分析 M2 相关基因和蛋白。我们还使用咪喹莫特（IMQ）诱导的银屑病小鼠模型研究了 Treg-of-B 细胞诱导的 M2 巨噬细胞对皮肤炎症的治疗作用。我们的研究结果表明，与 Treg-of-B 细胞共培养的 BMDM 上调了典型的 M2 相关分子，包括 Arg-1、IL-10、Pdcd1lg2、MGL-1、IL-4、YM1/2 和 CD206。在炎症环境中，与 Treg-of-B 细胞共培养的巨噬细胞中 TNF-α和 IL-6 的产生显著减少。分子机制表明，Treg-of-B 细胞通过细胞接触依赖的 STAT6 激活促进 M2 巨噬细胞极化。此外，用 Treg-of-B 细胞诱导的 M2 巨噬细胞治疗可减轻 IMQ 诱导的银屑病小鼠模型中的银屑病临床表现，如鳞屑、红斑和增厚。在 IMQ 应用后，Treg-of-B 细胞诱导的 M2 巨噬细胞组中引流淋巴结中的 T 细胞活化减少。综上所述，我们的研究结果表明，Foxp3 Treg-of-B 细胞可以通过 STAT6 激活诱导替代激活的 M2 巨噬细胞，为银屑病提供一种基于细胞的治疗策略。
